Chemical Properties
white to light yellow crystals
Uses
2-Chloro-N-methoxy-N-methylacetamide is used in the preparation of 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS) and structurally related 2-alkyl-4-quinolones having biological activity, 2-(benzo[d]thiazol-2-ylsulfonyl)-N-methoxy-N-methylacetamide and α-chloro-ketone, starting reagent for the one-pot synthesis of 2-heptyl-3-hydroxyl-4(1H)-quinolone (PQS), signaling molecule in the quorum sensing of Pseudomonas aeruginosa.
General Description
2-Chloro-
N-methoxy-
N-methylacetamide is a Weinreb amide.
Synthesis
Example 139 Synthesis of N-methoxy-N-methylchloroacetamide: N,O-dimethylhydroxylamine hydrochloride (200 g, 2.05 mol) was dissolved in tert-butyl methyl ether (2 L), and the solution was slowly added to an aqueous solution of potassium carbonate (624 g, 4.1 mol) (2 L) that was pre-cooled to 0 °C. The reaction mixture was further cooled to -5 °C, followed by the slow dropwise addition of chloroacetyl chloride, controlling the reaction temperature to not exceed 5 °C. After the dropwise addition, the reaction mixture was gradually warmed up to room temperature with continuous vigorous stirring for 3.5 hours. After completion of the reaction, the organic and aqueous phases were separated and the aqueous phase was extracted with tert-butyl methyl ether (3 x 1 L). All organic phases were combined, washed with saturated aqueous sodium chloride solution (2 x 1 L), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dried under vacuum to give a white solid product (257 g, 92% yield). The product was characterized by the following data: melting point 39-40.5 °C; 1H NMR (CDCl3, 300 MHz) δ 4.24 (s, 2H), 3.74 (s, 3H), 3.22 (s, 3H); mass spectra (CI) m/z 138 (MH+); elemental analysis (C4H8ClNO2) calculated values: C, 34.92; H, 5.86; N, 10.18; measured values. 10.18; measured values: C, 35.06; H, 5.88; N, 10.23.
References
[1] Journal of the American Chemical Society,
[2] Journal of the American Chemical Society, 2009, vol. 131, p. 1077 - 1091
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 27, p. 3917 - 3920
[4] RSC Advances, 2013, vol. 3, # 26, p. 10158 - 10162
[5] Patent: EP1054881, 2008, B1. Location in patent: Page/Page column 57
